Pristionchus trametes n. sp. (Diplogastridae) isolated from the mushroom Trametes orientalis in Kyoto, Japan.

A new species of Pristionchus was isolated from fruiting bodies of the wood-decaying fungus Trametes orientalis collected from Kyoto, Japan. Attempts to culture it using bacteria, yeast, and freeze-killed wax moth larvae as food or substrate failed. The eurystomatous form of the species was not found in the collected material, and the species is typologically characterized by: its 'small' stoma with thin, membrane-like cheilostomatal plates, a small triangular right subventral tooth, thorn-like dorsal tooth, and small left subventral denticles; a short, blunt male tail spike; and a short, conical female tail. Although the posterior probability support was not high (66%), phylogenetic analysis of both small and large ribosomal RNA gene subunits suggests that the species is closely related to P. elegans and P. bucculentus. The new species can be distinguished from those two by its diagnostic characters comprising the stomatal morphology and male and female tail characters.

Comparison of Sapwood Discoloration in Fagaceae Trees After Inoculation with Isolates of Raffaelea quercivora, Cause of Mass Mortality of Japanese Oak Trees.

The mass mortality of oak trees has been prevalent in Japan since the late 1980s. The fungus Raffaelea quercivora is transmitted by an ambrosia beetle, Platypus quercivorus, which causes mortality. The beetle is able to bore galleries into the sapwood of most Fagaceae trees in Japan; however, the level of mortality caused by R. quercivora and P. quercivorus differs greatly among tree species. Previous studies by our research group have demonstrated that the virulence of R. quercivora differs among isolates when inoculated into Quercus serrata logs. However, interactions between the virulence of R. quercivora isolates and the susceptibility of other fagaceous species have yet to be elucidated. In this study, we inoculated the fresh logs of 11 fagaceous species with isolates of low and high virulence, and measured the tangential widths of discolored sapwoods 3 weeks after inoculation. Although the discoloration widths of Q. crispula sapwood were similar among all isolates, those of Q. serrata and Q. acutissima tended to increase with the more virulent isolates. Sapwood discoloration in Q. glauca, Q. acuta, Q. salicina, Lethocarpus edulis, and Castanopsis sieboldii was greatly increased by highly virulent isolates. Discoloration in Fagus japonica was not influenced by any of the isolates. The logs of Q. crispula and Q. serrata but not Q. glauca were significantly more discolored by a low-virulence isolate compared with standing trees. The various virulent isolates induced unique sapwood discoloration characteristics in each species, which may explain species-specific differences in mortality rates.

Nematode and Strepsipteran Parasitism in Bait-Trapped and Hand-Collected Hornets (Hymenoptera, Vespidae, Vespa).

The parasitism of two groups of host-manipulating parasites of hornets was examined in Kyoto, Japan. Vespa mandarinia (661 individuals), V. simillima (303), V. analis (457), V. ducalis (158), V. crabro (57), and V. dybowskii (4) were collected either by bait trap or hand collection with an insect net, and examined for their parasites. An endoparasitic nematode, Sphaerularia vespae was isolated from three overwintered gynes of V. mandarinia and a gyne of V. ducalis. While endoparasitic insects, Xenos spp., were recovered from 13 V. mandarinia, 77 V. analis, two V. ducalis, and three V. crabro, and those recovered from V. analis and others were molecularly identified as X. oxyodontes and X. moutoni, respectively. Comparing Xenos parasitism level and capturing methods, the parasitism level was significantly higher in trapped hosts than in hand-collected ones, suggesting that stylopized hosts are more strongly attracted to the food source (bait trap) compared with unparasitized hosts. The genotypes of S. vespae were identical to each other, and near identical to its type population. While each of the two Xenos spp. showed four mitochondrial DNA haplotypes. A phylogenetic comparison suggested that Xenos haplotypes found in the present study are close to those previously reported from Japan and other Asian countries.

Influence of zinc deficiency to the mice infected with Babesia microti.

Zinc (Zn) is an essential trace element for DNA synthesis and for cell growth and differentiation. The deficiency induces a wide range of disorders including immunodeficiency. In this study, the influence of Zn deficiency to the mice infected with Babesia microti was examined, and was compared with the influence in the rats infected with B. rodhaini previously reported. Experiments of B. microti infection were conducted using Zn-deficient (ZD; allowed to eat ad libitum on the ZD diet), Zn-adequate (ZA; allowed to eat ad libitum on the ZA diet), and diet-restricted (DR; supplied 2 g/day on the ZA diet) mice. It was suggested that the Zn deficiency exacerbated the infection dynamics of the mice with B. microti by the growth retardation, the reduction of immunity and the decrease in PCV. The results in the mice supported the consequences in the rats previously reported.

Three Seinura species from Japan with a description of S. shigaensis n. sp. (Tylenchomorpha: Aphelenchoididae).

A preliminary survey of Seinura spp. was conducted in the Kyoto area, Western Japan. The survey yielded four new strains of Seinura spp., including two strains of S. caverna, a strain of S. italiensis, and a strain of an undescribed species. Molecularly, the two strains of S. caverna were nearly identical to the type strain but showed some minor variations, particularly in the mitochondrial cytochrome oxidase subunit I gene. The small subunit and D2-D3 large subunit sequences of the Japanese strain of S. italiensis were nearly identical and identical to its original description, respectively, and the difference in the small subunit was due to mis-reading of the sequences. The new species, S. shigaensis n. sp., was phylogenetically close to S. caverna and S. persica, although these three species were clearly different phylogenetically. The new species was typologically similar or nearly identical to several other Seinura spp., including S. chertkovi, S. christiei, S. italiensis, S. steineri, and S. tenuicaudata, but it can be distinguished from those species by the morphometric values. Because the new species is phylogenetically very close to S. caverna, it could be a good comparative system for S. caverna as a potential satellite model for the predatory nematode.

Effects of Dapagliflozin Compared with Sitagliptin and Metformin in Drug-Naïve Japanese Patients with Type 2 Diabetes: A 12-Week, Open-Label, Randomized, Active-Controlled Trial.

INTRODUCTION: To compare the efficacy and tolerability of dapagliflozin with those of sitagliptin and metformin in patients with type 2 diabetes who have never received glucose-lowering agents. METHODS: In this randomized, 12-week, open-label, active-controlled trial, 32 patients were randomly assigned to receive dapagliflozin 5 mg, sitagliptin 50 mg, or metformin 1000 mg per day for 12 weeks. At baseline and at week 12, the patients underwent a meal tolerance test (MTT). RESULTS: After 12 weeks of treatment, the changes in fasting and postprandial plasma glucose and plasma glucose area under the curve (AUC)0-120 min levels during the MTT from baseline were significantly improved in the three study groups, and there were no significant differences among the three study groups (P < 0.05). The mean changes in glycated hemoglobin (HbA1c) from baseline to week 12 were - 0.96%, - 1.24%, and - 1.40% in the dapagliflozin, sitagliptin, and metformin groups, respectively. Although there was no significant difference among the three study groups, the lowering effect of HbA1c tended to be greater in the metformin group than in the dapagliflozin group. In contrast, the insulin AUC0-120 min levels at week 12 significantly decreased only in the dapagliflozin group (P = 0.049). Similarly, body weight was significantly reduced only in the dapagliflozin group (- 2.1 kg [- 2.7%], P = 0.047). Moreover, dapagliflozin significantly improved serum adiponectin levels (P = 0.003). However, there were no significant differences in the changes in these glycemic and metabolic parameters among the three study groups. No serious adverse events were documented in any group. CONCLUSIONS: Dapagliflozin exerted beneficial effects similar to sitagliptin and metformin on glycemic parameters. In addition, dapagliflozin significantly reduced body weight and insulin AUC levels and improved serum adiponectin levels. Therefore, we suggest that these three hypoglycemic agents could be viable first-line medications for drug-naïve Japanese patients with type 2 diabetes. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN000024427).

Influence of zinc deficiency to the rats infected with Babesia rodhaini.

Zinc deficiency induces a wide range of disorders including immunodeficiency. It is known that microbial infections occur with a high frequency in the zinc-deficient hosts, but the study on the correlation between parasitic infection and zinc status in hosts is scarcely performed. We observed that the influence of zinc deficiency to the rats infected with Babesia rodhaini. Experiments of B. rodhaini infection were conducted using zinc-deficient (ZD; eat ad libitum or 10 g/day on the ZD diet), zinc-adequate (ZA; eat ad libitum on the ZA diet), and diet-restricted (DR; eat 7 g/day on the ZA diet) rats. The findings in this study suggested that the zinc deficiency had deleterious effects on the hemodynamics and mortality of the rats infected with B. rodhaini.

High dose of commercial products of kava (Piper methysticum) markedly enhanced hepatic cytochrome P450 1A1 mRNA expression with liver enlargement in rats.

Commercial products containing the kava plant (Piper methysticum), known to have the anxiolytic activity, are banned in several European countries and Canada because of the suspicion of a potential liver toxicity. In some reports, kava and kavalactones (major constituents of kava) inhibited activities of cytochrome P450 (CYP) isoforms including CYP1A2. On the other hand, a few studies showed that administration of kava to rats moderately increased CYP1A2 proteins in the liver. CYP1A isoforms are likely responsible for the metabolic activation of potent carcinogenic environmental toxins such as aflatoxins, benzo[a]pyrene, and others. On these bases, we have investigated the effects of administration of commercial kava products on gene expression of hepatic CYP1A isoforms in rats. A high dose (equivalent to approximately 380mg kavalactones/kg/day; 100 times of the suggested dosage for human use) of two different types of kava products for 8 days significantly increased liver weights. CYP1A2 mRNA expression was moderately increased (2.8-7.3 fold). More importantly, the high dose of kava markedly enhanced CYP1A1 mRNA expression (75-220 fold) as well as ethoxyresorufin O-deethylase activities and CYP1A1 immunoreactivities. Thus, no observed adverse effect levels of kavalactones would be lower than 380mg/kg/day. When the safety factor of kavalactones is assumed to be 100, a value most often used upon the risk analysis of chemicals and designed to account for interspecies and intraspecies variations, a number of kava product users likely ingest more kavalactones than acceptable daily intakes. Based on overall evidence, we should pay considerable attention to the possibility that kava products induce hepatic CYP1A1 expression in human especially in sensitive individuals.

Long-Term Effects of Ipragliflozin on Diabetic Nephropathy and Blood Pressure in Patients With Type 2 Diabetes: 104-Week Follow-up of an Open-Label Study.

BACKGROUND: In our previous study, we investigated the efficacy of ipragliflozin, a sodium-glucose cotransporter (SGLT) 2 inhibitor on diabetic nephropathy in patients with type 2 diabetes and demonstrated that ipragliflozin significantly improved diabetic nephropathy in addition to reducing HbA1c and body weight. Herein, we conducted post-trial monitoring to determine whether these lowering effects on blood glucose and body weight or the beneficial effects on diabetic nephropathy were maintained long-term (104 weeks) after starting ipragliflozin treatment. METHODS: Initially, during a 24-week interventional trial period, a 50 mg dose of ipragliflozin was administered to 50 patients with type 2 diabetes without changing other treatments. During the post-trial monitoring period, these patients returned to hospital-based diabetes care according to their clinical needs. We continued monitoring their clinical data for 104 weeks in each hospital and analyzed the results on an intention-to-treat basis. RESULTS: The improvements in glycemic control and body weight reduction provided by 24-week ipragliflozin administration were maintained for 104 weeks. Despite a transient decrease during the intervention period, the estimated glomerular filtration rate (eGFR) was restored to near the baseline level at 104 weeks. Notably, in patients with diabetic nephropathy, the median urinary albumin-to-creatinine ratio (UACR) was significantly decreased from 119.2 (98.9 - 201.8) at baseline to 36.9 (19.7 - 204.7) mg/gCr at 104 weeks. In addition, eGFR was stable for 104 weeks, showing no decrease. In contrast, a significant positive correlation between UACR and blood pressure observed at 24 weeks disappeared after discontinuation of the intervention therapy. CONCLUSIONS: The well-controlled HbA1c and body weight reductions were maintained for 104 weeks of post-trial follow-up. Moreover, ipragliflozin significantly reduced urinary albumin excretion in patients with diabetic nephropathy without decreasing eGFR.